Respiratory tract infection is one of the communicable diseases that are relatively hard to control in animal husbandry, and has serious damage to animal husbandry. When respiratory infections are prevalent, huge economic losses is made to animal husbandry. Thus, how to prevent respiratory infections in livestock such as pigs and cattle is an important research topic for veterinarians and veterinary workers. Since respiratory tract infections are generally multiple infections with numerous pathogenic factors and complicated disease conditions, there is currently no effective prevention method. For animal respiratory infections, while seeking biological control and environmental protection, medical treatment is still the main current approach. The search for an effective, safe, broad-spectrum, high-efficiency and low-residue new antimicrobial agent for respiratory infections is an important direction for the research and development of veterinary drugs.
Tulathromycin, which was developed by Pfizer (U.S.A.), is a macrolide semi-synthetic antibiotic specially for animals, and the chemical structure of which is represented by formula I. Tulathromycin is mainly used for the prevention and treatment of respiratory diseases in pigs and cattle caused by actinobacillus pleuropneumoniae, mycoplasma, pasteurella, haemophilus paracasei and so on. Especially for the treatment of respiratory system disease of cattle and pigs, there is a very obvious efficacy. Because there are three amino groups in the structure of tulathromycin, it has numerous advantages such as rapid absorption, low dosage, long-lasting efficacy, and single-administration for full-course treatment. Since its launch, it has received extensive attention from the veterinary drug industry at home and abroad.

Tulathromycin product-Draxxin is composed of two isomers when it reaches equilibrium in aqueous solution. One is a 15-membered azalides-tulathromycin A (formula I), and the other is a 13-membered azalides-tulathromycin B (Formula I′), and the contents of which are respectively 90% and 10%. Since there is a phenomenon in which two isomers of tulathromycin are balanced in a solution (i.e., a tulathromycin solution, the solute is tulathromycin, and the solvent is selected from the group consisting of water, organic solvent and mixed solvent of water and organic solvent), changes of the solution environment and pH greatly affects the ratio of these two components which imposes higher requirements on preparations. Due to different biological activities of the two isomers, the efficacy of the drug to animals is also affected. Pfizer discloses a method in U.S. Pat. No.6,825,327B2, comprising: in isopropanol solvent, performing a ring-opening reaction by using an epoxidation intermediate and n-propylamine to obtain crude tulathromycin, reacting the crude tulathromycin with phosphoric acid to form a salt, then alkalizing, and recrystallizing to obtain tulathromycin. However, due to the salt formation reaction of crude tulathromycin and phosphoric acid is performed in a mixed solution of organic solvent and water, i.e., there is water in the system of recrystallization process, and due to residue of n-propylamine, the amount of phosphoric acid used is not easy to be precise, and the duration of the recrystallization is long, leading to glycosidic bond cleavage of tulathromycin, resulting in the increase of impurities. In addition, after the subsequent alkalization, the yield and purity of the recrystallized product from dichloromethane/n-heptane system are low, and the impurity removal effect is not obvious. Therefore, there is a need in the art for a method of preparing high-purity tulathromycin.
